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Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.
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Escarlatina , Infecciones Estreptocócicas , Humanos , Streptococcus pyogenes/genética , Escarlatina/epidemiología , Alelos , Inglaterra/epidemiología , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/epidemiología , Reacción en Cadena de la Polimerasa , Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genéticaRESUMEN
Ototoxic drugs such as aminoglycoside antibiotics and cisplatin (CDDP) can cause sensorineural hearing loss (SNHL), which is closely related to oxidative stress and the acidification of the inner ear microenvironment. Effective treatment of SNHL often requires multifaceted approach due to the complex pathology, and drug combination therapy is expected to be at the forefront of modern hearing loss treatment. Here, space-station-like composite nanoparticles (CCC@mPP NPs) with pH/oxidation dual responsiveness and multidrug simultaneous delivery capability were constructed and then loaded with various drugs including panax notoginseng saponins (PNS), tanshinone IIA (TSIIA), and ammonia borane (AB) to provide robust protection against SNHL. Molecular dynamics simulation revealed that carboxymethyl chitosan/calcium carbonate-chitosan (CCC) NPs and monomethoxy poly(ethylene glycol)-PLGA (mPP) NPs can rendezvous and dock primarily by hydrogen bonding, and electrostatic forces may be involved. Moreover, CCC@mPP NPs crossed the round window membrane (RWM) and entered the inner ear through endocytosis and paracellular pathway. The docking state was basically maintained during this process, which created favorable conditions for multidrug delivery. This nanosystem was highly sensitive to pH and reactive oxygen species (ROS) changes, as evidenced by the restricted release of payload at alkaline condition (pH 7.4) without ROS, while significantly promoting the release in acidic condition (pH 5.0 and 6.0) with ROS. TSIIA/PNS/AB-loaded CCC@mPP NPs almost completely preserved the hair cells and remained the hearing threshold shift within normal limits in aminoglycoside- or CDDP-treated guinea pigs. Further experiments demonstrated that the protective mechanisms of TSIIA/PNS/AB-loaded CCC@mPP NPs involved direct and indirect scavenging of excessive ROS, and reduced release of pro-inflammatory cytokines. Both in vitro and in vivo experiments showed the high biocompatibility of the composite NPs, even after long-term administration. Collectively, this work suggests that composite NPs is an ideal multi-drug-delivery vehicle and open new avenues for inner ear disease therapies.
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Quitosano , Pérdida Auditiva Sensorineural , Nanopartículas , Animales , Cobayas , Ácido Láctico/química , Quitosano/química , Hidrógeno , Medicina Tradicional China , Especies Reactivas de Oxígeno , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Cisplatino , Nanopartículas/química , AminoglicósidosRESUMEN
Taste peptides are oligopeptides that enhance both aroma and taste of food, and they are classified into five categories based on their taste characteristics: salty, sour, umami, sweet, bitter, and kokumi peptide. Recently, taste peptides have attracted the attention of several fields of research in food science and commercial applications. However, research on taste receptors of taste peptides and their taste transduction mechanisms are not clearly understood and we present a comprehensive review about these topics here. This review covers the aspects of taste peptides perceived by their receptors in taste cells, the proposed transduction pathway, as well as structural features of taste peptides. Apart from traditional methods, molecular docking, peptidomic analysis, cell and animal models and taste bud biosensors can be used to explore the taste mechanism of taste peptides. Furthermore, synergistic effect, Maillard reaction, structural modifications and changing external environment are employed to improve the taste of taste peptides. Consequently, we discussed the current challenges and future trends in taste peptide research. Based on the summarized developments, taste peptides derived from food proteins potentially appear to be important taste substances. Their applications meet the principles of "safe, nutritious and sustainable" in food development.
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In recent years, cloud-native technology has become popular among Internet companies. Microservice architecture solves the complexity problem for multiple service methods by decomposing a single application so that each service can be independently developed, independently deployed, and independently expanded. At the same time, domestic industrial Internet construction is still in its infancy, and small and medium-sized enterprises still face many problems in the process of digital transformation, such as difficult resource integration, complex control equipment workflow, slow development and deployment process, and shortage of operation and maintenance personnel. The existing traditional workflow architecture is mainly aimed at the cloud scenario, which consumes a lot of resources and cannot be used in resource-limited scenarios at the edge. Moreover, traditional workflow is not efficient enough to transfer data and often needs to rely on various storage mechanisms. In this article, a lightweight and efficient workflow architecture is proposed to optimize the defects of these traditional workflows by combining cloud-edge scene. By orchestrating a lightweight workflow engine with a Kubernetes Operator, the architecture can significantly reduce workflow execution time and unify data flow between cloud microservices and edge devices.
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Programas Informáticos , Tecnología , Flujo de TrabajoRESUMEN
This paper introduces a novel method for enhancing fault classification and diagnosis in dynamic nonlinear processes. The method focuses on dynamic feature extraction within multivariate time series data and utilizes dynamic reconstruction errors to augment the feature set. A fault classification procedure is then developed, using the weighted maximum scatter difference (WMSD) dimensionality reduction criterion and quadratic discriminant analysis (QDA) classifier. This method addresses the challenge of high-dimensional, sample-limited fault classification, offering early diagnosis capabilities for online samples with smaller amplitudes than the training set. Validation is conducted using a cold rolling mill simulation model, with performance compared to classical methods like linear discriminant analysis (LDA) and kernel Fisher discriminant analysis (KFD). The results demonstrate the superiority of the proposed method for reliable industrial process monitoring and fault diagnosis.
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OBJECTIVE: To explore the associations between dietary tastes and chronic diseases quantitatively. DESIGN: We used the Geodetector method to establish associations between seven tastes and a variety of chronic diseases from the perspective of spatial stratified heterogeneity and explained the effects of dietary tastes on the spatial distribution of chronic diseases. SETTING: We used crowdsourcing online recipe data to extract multiple taste information about cuisines, combined with point of interest data on categorised restaurant data in different regions, to quantitatively analyse the taste preferences of people in different regions. PARTICIPANTS: Crowdsourcing online recipe data and restaurant data in different regions. RESULTS: The results showed that sixteen diseases were significantly associated with dietary tastes among the seventy-one types of chronic diseases. Compared with the effects of individual tastes, the interactions of tastes increased the risk of sixteen diseases, and many combinations of tastes produced nonlinear enhancement effects on the risk for diseases. CONCLUSIONS: This study presents a quantitative study approach based on the crowdsourcing of data to explore potential health risk factors, which can be applied to the exploratory analysis of disease aetiology and help public health authorities to develop corresponding interventions.
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Preferencias Alimentarias , Gusto , Enfermedad Crónica , Dieta , Humanos , Percepción del GustoRESUMEN
Contraction stimulates skeletal muscle glucose uptake predominantly through activation of AMP-activated protein kinase (AMPK) and Rac1. However, the molecular details of how contraction activates these signaling proteins are not clear. Recently, Axin1 has been shown to form a complex with AMPK and liver kinase B1 during glucose starvation-dependent activation of AMPK. Here, we demonstrate that electrical pulse-stimulated (EPS) contraction of C2C12 myotubes or treadmill exercise of C57BL/6 mice enhanced reciprocal coimmunoprecipitation of Axin1 and AMPK from myotube lysates or gastrocnemius muscle tissue. Interestingly, EPS or exercise upregulated total cellular Axin1 levels in an AMPK-dependent manner in C2C12 myotubes and gastrocnemius mouse muscle, respectively. Also, direct activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide treatment of C2C12 myotubes or gastrocnemius muscle elevated Axin1 protein levels. On the other hand, siRNA-mediated Axin1 knockdown lessened activation of AMPK in contracted myotubes. Further, AMPK inhibition with compound C or siRNA-mediated knockdown of AMPK or Axin1 blocked contraction-induced GTP loading of Rac1, p21-activated kinase phosphorylation, and contraction-stimulated glucose uptake. In summary, our results suggest that an AMPK/Axin1-Rac1 signaling pathway mediates contraction-stimulated skeletal muscle glucose uptake.
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Proteínas Quinasas Activadas por AMP/fisiología , Proteína Axina/fisiología , Glucosa/metabolismo , Contracción Muscular/fisiología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiología , Neuropéptidos/fisiología , Transducción de Señal/fisiología , Proteína de Unión al GTP rac1/fisiología , Proteínas Quinasas Activadas por AMP/genética , Animales , Proteína Axina/genética , Línea Celular , Estimulación Eléctrica , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Ratones Endogámicos C57BL , Neuropéptidos/genética , ARN Interferente Pequeño/farmacología , Transducción de Señal/genética , Proteína de Unión al GTP rac1/genéticaRESUMEN
Objective.The scarcity of electroencephalogram (EEG) data, coupled with individual and scenario variations, leads to considerable challenges in real-world EEG-based driver fatigue detection. We propose a domain adaptation method that utilizes EEG data collected from a laboratory to supplement real-world EEG data and constructs a cross-scenario and cross-subject driver fatigue detection model for real-world scenarios.Approach.First, we collect EEG data from subjects participating in a driving experiment conducted in both laboratory and real-world scenarios. To address the issue of data scarcity, we build a real-world fatigued driving detection model by integrating the real-world data with the laboratory data. Then, we propose a method named cross-scenario and cross-subject domain adaptation (CS2DA), which aims to eliminate the domain shift problem caused by individual variances and scenario differences. Adversarial learning is adopted to extract the common features observed across different subjects within the same scenario. The multikernel maximum mean discrepancy (MK-MMD) method is applied to further minimize scenario differences. Additionally, we propose a conditional MK-MMD constraint to better utilize label information. Finally, we use seven rules to fuse the predicted labels.Main results.We evaluate the CS2DA method through extensive experiments conducted on the two EEG datasets created in this work: the SEED-VLA and the SEED-VRW datasets. Different domain adaptation methods are used to construct a real-world fatigued driving detection model using data from laboratory and real-world scenarios, as well as a combination of both. Our findings show that the proposed CS2DA method outperforms the existing traditional and adversarial learning-based domain adaptation approaches. We also find that combining data from both laboratory and real-world scenarios improves the performance of the model.Significance.This study contributes two EEG-based fatigue driving datasets and demonstrates that the proposed CS2DA method can effectively enhance the performance of a real-world fatigued driving detection model.
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Conducción de Automóvil , Electroencefalografía , Fatiga , Humanos , Electroencefalografía/métodos , Fatiga/diagnóstico , Fatiga/fisiopatología , Masculino , Adulto , Femenino , Adulto JovenRESUMEN
BACKGROUND: The occurrence and progression of hepatocellular carcinoma (HCC) are significantly affected by DNA damage response (DDR). Exploring DDR-related biomarkers can help predict the prognosis and immune characteristics of HCC. METHODS: First, the single-cell RNA sequencing (scRNA-seq) dataset GSE242889 was processed and performed manual annotation. Then we found the marker genes of DDR-active subgroups based on "AUCell" algorithm. The "Limma" R package was used to identify differentially expressed genes (DEGs) between tumor and normal samples of HCC. The risk prognostic model was constructed by filtering genes using univariate Cox and LASSO regression analyses. Finally, the signatures were analyzed for immune infiltration, gene mutation, and drug sensitivity. Last but not least, KPNA2, which had the largest coefficient in our model was validated by experiments including western blot, MTT, colony formation and γ-H2AX assays. RESULTS: We constructed a prognostic model based on 5 DDR marker genes including KIF2C, CDC20, KPNA2, UBE2S and ADH1B for HCC. We also proved that the model had an excellent performance in both training and validation cohorts. Patients in the high-risk group had a poorer prognosis, different immune features, gene mutation frequency, immunotherapy response and drug sensitivity compared with the low-risk group. Besides, our experimental results proved that KPNA2 was up-regulated in liver cancer cells than in hepatocytes. More importantly, the knockdown of KPNA2 significantly inhibited cell variability, proliferation and promoted DNA damage. CONCLUSIONS: We innovatively integrated scRNA-seq and bulk RNA sequencing to construct the DDR-related prognostic model. Our model could effectively predict the prognosis, immune landscape and therapy response of HCC.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Daño del ADN , Neoplasias Hepáticas , Análisis de la Célula Individual , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Pronóstico , Daño del ADN/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Análisis de Secuencia de ARNRESUMEN
Background: The COVID-19 pandemic has presented unique challenges to individuals worldwide, with a significant focus on the impact on sleep. However, the precise mechanisms through which emotional and cognitive variables mediate this relationship remain unclear. To expand our comprehensive understanding of variables, the present study utilizes the Preventive Stress Management theory, to test the relationship between perceived social support and sleep quality, as well as the effect of perceived COVID-19 stress, hope, negative emotions and coping styles. Methods: Data were collected in March 2022 from 1,034 college students in two universities located in Liaoning Province, China, using an online survey platform regarding perceived social support, perceived COVID-19 stress, sleep quality, hope, negative emotions and coping styles. The moderated mediation model were conducted using Process macro program (Model 6) and the syntax in SPSS. Results: The results revealed perceived COVID-19 stress and negative emotions sequentially mediated the negative relationship between perceived social support and sleep quality. Furthermore, hope and coping styles were found to moderate the sequential mediating effect. Conclusion: The present study sheds light on the pathways that affect sleep quality among college students during the COVID-19 pandemic. Findings highlight the protective roles played by positive social and personal resources, such as perceived social support, hope, and effective coping styles, against sleep problems. These insights have important implications for the development of targeted interventions to improve sleep outcomes during this challenging time.
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COVID-19 , Pandemias , Calidad del Sueño , Estrés Psicológico , COVID-19/epidemiología , Estrés Psicológico/prevención & control , Estrés Psicológico/psicología , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Apoyo Social , Habilidades de Afrontamiento , Esperanza , Emociones , China/epidemiología , Universidades , Encuestas y Cuestionarios , Internet , Análisis de Mediación , Estudiantes/psicología , Análisis de Regresión , PercepciónRESUMEN
The microstructure at the interface between the cocatalyst and semiconductor plays a vital role in concentrating photo-induced carriers and reactants. However, observing the atomic arrangement of this interface directly using an electron microscope is challenging due to the coverings of the semiconductor and cocatalyst. To address this, multiple metal-semiconductor interfaces on three TiO2 crystal facets (M/TiO2 âN, where M represents Ag, Au, and Pt, and N represents the 001, 010, and 101 single crystal facets). The identical surface atomic configuration of the TiO2 facets allowed us to investigate the evolution of the microstructure within these constructs using spectroscopies and DFT calculations. For the first time, they observed the transformation of saturated Ti6c âO bonds into unsaturated Ti5c âO and Ti6c âOâPt bonds on the TiO2 â010 facet after loading Pt. This transformation have a direct impact on the selectivity of the resulting products, leading to the generation of CO and CH4 at the Ti6c âOâPt and Pt sites, respectively. These findings pinpoint the pivotal roles played by the atomic arrangement at the M/TiO2 âN interfaces and provide valuable insights for the development of new methodologies using conventional lab-grade equipment.
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Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC). US33A-mediated DMXL1 degradation inhibits lysosome acidification and autophagic cargo degradation. Formation of the virion assembly compartment, which requires lysosomes, occurs significantly later with US33A-expressing virus infection, with reduced viral replication. These data thus identify a viral strategy for cellular remodeling, with the potential to employ US33A in therapies for viral infection or rheumatic conditions, in which inhibition of lysosome acidification can attenuate disease.
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Citomegalovirus , Proteómica , Humanos , Citomegalovirus/fisiología , Ensamble de Virus , Replicación Viral , Proteínas , Autofagia , Lisosomas , Concentración de Iones de HidrógenoRESUMEN
This article constructed a food taste deviation index using text analysis based on food culture as a measure of cultural inclusion. Cultural inclusion was related to corporate total factor productivity, aiming to investigate whether the cultural inclusion affects corporate sustainability. The findings showed uneven distribution of cultural inclusion in various areas of China, contributing to the unbalanced sustainable development of firms in different regions, as reflected by the higher total factor productivity of firms located in regions with higher cultural inclusion. A test using mountainous undulation as an instrumental variable verified the causal relationship between cultural inclusion and firm sustainability. Besides, a regression discontinuity design was employed to mitigate the impacts of the bidirectional causality. Moreover, a high level of cultural inclusion in top managers' hometown significantly improved corporate sustainability, suggesting that executives can transmit cultural inclusion in society. In addition, firms in more inclusive regions are more motivated to increase their social responsibility to staff as a way to promote their total factor productivity, suggesting that cultural inclusion promotes firm sustainability by increasing firms' care for staff. This article also found that cultural inclusion has heterogeneous effects across firms of different levels of industry competition, and different levels of analyst attention. The research reveals the impact of cultural inclusion on the real economy and help academics dissect the informal institutional reasons behind the sustainable development of firms in different geographies from a new perspective, contributing to the promotion of economic sustainability at the regional level and related policy formulation.
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Levan is a high-valued ß-(2,6)-linked fructan with promising physicochemical and physiological properties and has diverse potential applications in the food, nutraceutical, pharmaceutical and cosmetic industry, but its commercial availability is still restricted to the relatively high costs of production. In this study, a strain identified as Microbacterium sp. XL1 was isolated from soil and highly produced exopolysaccharide (EPS). HPLC, FTIR and NMR spectroscopy revealed XL1-EPS is a levan-type fructan connected by ß-(2, 6) linkages. SEM, DLS and TGA-DSC analysis showed that XL1-EPS processed high morphological versatility, narrow size distribution in its solutions and excellent thermal stability. The levan yield reached 83.67 ± 4.06 g/L with corresponding productivity of 3.49 ± 0.17 g/L/h and a conversion yield of 39.8 ± 1.9 % using sucrose (210 g/L) as substrates under the optimal cultivation conditions concluded by the response surface methodology (RSM). More strikingly, the XL1 strain also has multi-type fructanases to generate levanbiose, kestose, DFA IV and other L-FOSs. These results suggest Microbacterium sp. XL1 is a promising strain to produce levan and can provide various levan/inulin-degrading enzymes to create a great diversity of FOSs.
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Oysters are nutritious and tasty but difficult to store. Drying can extend the storage period of oysters and give them a unique flavor. In this study, the effects of four drying procedures, namely, vacuum freeze drying (VFD), vacuum drying (VD), natural sun-drying (NSD), and hot air drying (HAD), on the flavor characteristics of oysters (Crassostrea hongkongensis) were investigated using blanched oysters as a control (CK). Results showed that HAD produced more free amino acids than the other methods, but VFD retained the most flavor nucleotides. Compared with cold drying (VFD), hot drying (VD, NSD, and HAD) increased the abundance of organic acids, betaine, and aroma substances. Glutamic acid, alanine, AMP, hexanal, octanal, heptanal, (E, E)-2,4-heptadienal, (E)-2-decenal, nonanal, etc., are defined as the characteristic flavor compounds of dried oysters, with umami, sweet, green, fatty, and fruity aromas being the main organoleptic attributes of dried oysters. Glutamic acid, glycine, betaine, IMP, pentanal, ethyl heptanoate, (E, Z)-2,4-nonadienal, 1-octen-3-one, 2-hexenal, 2-octenal, hexanal, decanal were defined as markers to distinguish different drying methods. Overall, HAD showed improved flavor qualities and characteristics and was better suited for the highly commercialized production of dried oysters.
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OBJECTIVE: The objective of this study was to understand the molecular transmission characteristics of newly reported HIV infections in the city of Pengzhou, Sichuan Province, to analyze the risk factors of transmission network and spatial clustering and the transmission characteristics, and to provide a scientific basis for precision prevention and intervention. METHODS: Anticoagulated whole blood was collected from newly reported HIV infections in Pengzhou from March 2019 to August 2021. After the plasma was isolated, the HIV-1 pol gene was amplified and sequenced by reverse transcriptase polymerase chain reaction (PCR). The obtained gene sequences were used to construct a maximum likelihood phylogenetic tree for the analysis of virus subtypes, and a molecular transmission network was constructed using the genetic distance method to evaluate the transmission pattern of people living with HIV/AIDS in Pengzhou. A logistic regression model was used to find out the potential risk factors for entering the molecular transmission network with the number of nodes ≥ 2. Spatial analysis is used to show the geographical pattern of the proportion of newly reported HIV infections entering the molecular transmission network, and a flow map is used to show the intensity of transmission within and between townships. RESULTS: A total of 463 newly reported HIV-infection sequences were obtained in this study, including 237 cases (51.19%) of CRF01_ AE, 159 cases (34.34%) of CRF07_BC, 45 cases (9.72%) of B, 15 cases (3.24%) of CRF08_BC and 7 cases (1.5%) of others. The number of clusters was the highest when the gene distance was 0.009, with a total of 246 sequences entering the network, forming 54 clusters, and the network entry rate was 55.36%. There were 170 sequences with more than two nodes in the network sequence. The logistic regression showed that compared with age < 50 years old, age ≥ 50 years old has a higher risk of transmission (OR = 3.43, 95% CI = 2.06-5.71); compared with farmers, the risk of transmission within industry is lower (OR = 0.046, 95% CI = 0.25-0.87); and compared with CRF07_BC, CRF01_AE (OR = 6.09, 95% CI = 3.60-10.30) and B (OR = 20.31, 95% CI = 8.94-46.13) had a higher risk of transmission. Men aged ≥ 50 years are mainly clustered with women between 50 and 70 years of age. In addition to being clustered with gay men, there are nine (50%) and three (16.7%) chains of transmission between gay men and heterosexual men and women, respectively. In the geographical space, there is no hot spot clustering of the molecular propagation network. The subtype B was mainly distributed in the town of Tianpeng and formed transmission networks in eastern Pengzhou;0020CRF01_AE is mainly distributed in the town of Lichun and formed transmission networks in the west and north of Pengzhou. CONCLUSION: This study reveals the characteristics and influencing factors of molecular network transmission in the region, as well as the spatial transmission characteristics of newly reported HIV infections in recent years, and reveals the geographical differences in HIV-1 transmission. The results provide a scientific basis for the development of local AIDS-specific intervention measures.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Filogenia , VIH-1/genética , Genómica , Epidemiología Molecular , Genotipo , China/epidemiologíaRESUMEN
Streptococcus pyogenes genotype emm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm1 sublineage, M1UK, that produces increased levels of SpeA toxin was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UK is now dominant in England. To more fully characterize M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UK and contemporary non-M1UK emm1 strains (M1global). Just seven genes were differentially expressed by M1UK compared with contemporary M1global strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK (gldA, mipB/talC, pflD, and phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of gldA in M1global abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediate emm1 sublineages in England comprising 13/27 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogenetic emm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically defined medium. In rich broth, however, expression of SpeA was upregulated ~10-fold in both M123SNPs and M1UK sublineages, compared with M113SNPs and M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UK and undoubtedly important, M1UK strains have outcompeted M123SNPs and other emm types that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SNPs has contributed to a wider fitness advantage in M1UK on an inherently successful emm1 streptococcal background.
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Proteómica , Streptococcus pyogenes , Streptococcus pyogenes/genética , Filogenia , Antígenos Bacterianos/genética , InglaterraRESUMEN
Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout MVA infection of human fibroblasts and macrophages. >690 human proteins are down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets are not shared with replication-competent vaccinia. Viral intermediate/late gene expression is necessary for MVA antagonism of innate immunity, and suppression of interferon effectors such as ISG20 potentiates virus gene expression. Proteomic changes specific to infection of macrophages indicate modulation of the inflammatory response, including inflammasome activation. Our approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.
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Vaccinia , Humanos , Proteoma , Proteómica , Virus Vaccinia/genética , Muerte Celular , AntiviralesRESUMEN
Urban sprawl is thought to be a risk factor for childhood obesity primarily because the physical environment it creates discourages children's physical activity while encouraging their sedentary behavior. However, there has not been any review on the association between urban sprawl and childhood obesity. This study filled this research gap by comprehensively reviewing literature focusing on associations between urban sprawl and weight-related behaviors and outcomes among children and adolescents. Only two longitudinal and three cross-sectional studies conducted in two countries were identified. Sample sizes ranged from 2324 to 129 781. Four studies used weight status, and only one study used both behaviors and weight status as outcome variables. All positive, negative, and non-significant associations were reported. This review could not identify a clear association between urban sprawl and childhood obesity. More longitudinal studies are needed for in-depth analyses on this important topic in more regions, which would be important not only for public health guidelines but also for research, practice, and policies in urban planning.
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Obesidad Infantil , Adolescente , Niño , Estudios Transversales , Ambiente , Ejercicio Físico , Humanos , Obesidad Infantil/epidemiología , Factores de RiesgoRESUMEN
To control and prevent the risk of diabetes, diabetes studies have identified the need to better understand and evaluate the associations between influencing indicators and the prevalence of diabetes. One constraint has been that influencing indicators have been selected mainly based on subjective judgment and tested using traditional statistical modeling methods. We proposed a framework new to diabetes studies using data-driven and spatial methods to identify the most significant influential determinants of diabetes automatically and estimated their relationships. We used data from diabetes mellitus patients' health insurance records in Shandong province, China, and collected influencing indicators of diabetes prevalence at the county level in the sociodemographic, economic, education, and geographical environment domains. We specified a framework to identify automatically the most influential determinants of diabetes, and then established the relationship between these selected influencing indicators and diabetes prevalence. Our autocorrelation results showed that the diabetes prevalence in 12 Shandong cities was significantly clustered (Moran's I = 0.328, p < 0.01). In total, 17 significant influencing indicators were selected by executing binary linear regressions and lasso regressions. The spatial error regressions in different subgroups were subject to different diabetes indicators. Some positive indicators existed significantly like per capita fruit production and other indicators correlated with diabetes prevalence negatively like the proportion of green space. Diabetes prevalence was mainly subjected to the joint effects of influencing indicators. This framework can help public health officials to inform the implementation of improved treatment and policies to attenuate diabetes diseases.